Genetic Variant ATP6V0B:c.116+13A>G (chr1-43975861-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004047.5(ATP6V0B):c.116+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,587,268 control chromosomes in the GnomAD database, including 3,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.070 ( 430 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2885 hom. )

Consequence

ATP6V0B
NM_004047.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.291

Publications

15 publications found

Variant links:

Genes affected

ATP6V0B (HGNC:861): (ATPase H+ transporting V0 subunit b) This gene encodes a portion of the V0 domain of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Activity of this enzyme is necessary for such varied processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ATP6V0B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004047.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP6V0B	NM_004047.5	MANE Select	c.116+13A>G	intron	N/A	NP_004038.1	Q99437-1
ATP6V0B	NM_001294333.2		c.116+13A>G	intron	N/A	NP_001281262.1	E9PNL3
ATP6V0B	NM_001039457.3		c.-25-229A>G	intron	N/A	NP_001034546.1	Q99437-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP6V0B	ENST00000472174.7	TSL:1 MANE Select	c.116+13A>G	intron	N/A	ENSP00000431605.1	Q99437-1
ATP6V0B	ENST00000468183.5	TSL:1	n.878+13A>G	intron	N/A
ATP6V0B	ENST00000532642.5	TSL:2	c.116+13A>G	intron	N/A	ENSP00000434729.1	E9PNL3

Frequencies

GnomAD3 genomes

AF:

0.0699

AC:

10624

AN:

152084

Hom.:

429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0964

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0714

Gnomad ASJ

AF:

0.0485

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.0779

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0533

Gnomad OTH

AF:

0.0775

GnomAD2 exomes

AF:

0.0679

AC:

15722

AN:

231558

AF XY:

0.0675

show subpopulations

Gnomad AFR exome

AF:

0.0929

Gnomad AMR exome

AF:

0.0747

Gnomad ASJ exome

AF:

0.0408

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0521

Gnomad OTH exome

AF:

0.0637

GnomAD4 exome

AF:

0.0582

AC:

83489

AN:

1435066

Hom.:

2885

Cov.:

AF XY:

0.0583

AC XY:

41452

AN XY:

711448

show subpopulations

African (AFR)

AF:

0.0956

AC:

3094

AN:

32374

American (AMR)

AF:

0.0730

AC:

2998

AN:

41078

Ashkenazi Jewish (ASJ)

AF:

0.0448

AC:

1104

AN:

24652

East Asian (EAS)

AF:

0.163

AC:

6429

AN:

39322

South Asian (SAS)

AF:

0.0752

AC:

6245

AN:

83002

European-Finnish (FIN)

AF:

0.0297

AC:

1562

AN:

52668

Middle Eastern (MID)

AF:

0.0502

AC:

282

AN:

5612

European-Non Finnish (NFE)

AF:

0.0528

AC:

57910

AN:

1097212

Other (OTH)

AF:

0.0653

AC:

3865

AN:

59146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

3878

7755

11633

15510

19388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2356

4712

7068

9424

11780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0699

AC:

10642

AN:

152202

Hom.:

430

Cov.:

AF XY:

0.0705

AC XY:

5249

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0964

AC:

4004

AN:

41530

American (AMR)

AF:

0.0717

AC:

1096

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0485

AC:

168

AN:

3466

East Asian (EAS)

AF:

0.166

AC:

860

AN:

5168

South Asian (SAS)

AF:

0.0782

AC:

377

AN:

4822

European-Finnish (FIN)

AF:

0.0290

AC:

307

AN:

10594

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0533

AC:

3622

AN:

68008

Other (OTH)

AF:

0.0805

AC:

170

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

510

1020

1531

2041

2551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0584

Hom.:

375

Bravo

AF:

0.0732

Asia WGS

AF:

0.126

AC:

438

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.1

(source)

DANN

Benign

0.83

PhyloP100

-0.29

PromoterAI

0.13

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over